Assessment of Corticosteroid Therapy and Death or Disability According to Pretreatment Risk of Death or Bronchopulmonary Dysplasia in Extremely Preterm Infants
Authors: Erik A. Jensen, Laura Elizabeth Wiener, Matthew A. Rysavy, Kevin C. Dysart, Marie G. Gantz, Eric C. Eichenwald, Rachel G. Greenberg, Heidi M. Harmon, Matthew M. Laughon, Kristi L. Watterberg, Michele C. Walsh, Bradley A. Yoder, Scott A. Lorch, Sara B. DeMauro, Richard A. Polin, Abbot R. Laptook, Martin Keszler, Betty R. Vohr, Angelita M. Hensman, Elisa Vieira, Lucille St. Pierre, Robert T. Burke, Barbara Alksninis, Andrea Knoll, Mary L. Keszler, Teresa M. Leach, Elisabeth C. McGowan, Victoria E. Watson, Anna Maria Hibbs, Nancy S. Newman, Deanne E. Wilson-Costello, Bonnie S. Siner, Harriet G. Friedman, William E. Truog, Eugenia K. Pallotto, Howard W. Kilbride, Cheri Gauldin, Anne Holmes, Kathy Johnson, Allison Scott, Prabhu S. Parimi, Lisa Gaetano, Stephani L. Merhar, Kurt Schibler, Brenda B. Poindexter, Kimberly Yolton, Tanya E. Cahill, Teresa L. Gratton, Cathy Grisby, Kristin Kirker, Sandra Wuertz, Michael C. Cotten, Ronald N. Goldberg, Ricki F. Goldstein, William F. Malcolm, Patricia L. Ashley, Deesha Mago-Shah, Joanne Finkle, Kimberley A. Fisher, Kathryn E. Gustafson, Carl L. Bose, Janice Bernhardt, Gennie Bose, Janice Wereszczak, Diane Warner, Jennifer Talbert, Stephen D. Kicklighter, Alexandra Bentley, Laura Edwards, Ginger Rhodes-Ryan, Donna White, Ravi M. Patel, David P. Carlton, Yvonne Loggins, Ira Adams-Chapman (deceased), Diane Bottcher, Sheena L. Carter, Ellen C. Hale, Salathiel Kendrick-Allwood, Maureen Mulligan LaRossa, Colleen Mackie, Amy Sanders, Gloria Smikle, Lynn Wineski, Andrew A. Bremer, Rosemary D. Higgins, Stephanie Wilson Archer, Gregory M. Sokol, Heidi Harmon, Lu Ann Papile, Dianne E. Herron, Abbey C. Hines, Carolyn Lytle, Lucy Smiley, Leslie Dawn Wilson, Jon E. Tyson, Amir M. Khan, Kathleen A. Kennedy, Barbara J. Stoll, Riciardo A. Mosquera, Andrea F. Duncan, Emily Stephens, Elizabeth Allain, Julie Arldt-McAlister, Fatima Boricha, Katrina Burson, Allison G. Dempsey, Patricia W. Evans, Carmen Garcia, Donna J. Hall, Margarita Jiminez, Janice John, Patrick M. Jones, M. Layne Lillie, Karen Martin, Sara C. Martin, Georgia E. McDavid, Shannon L. McKee, Michelle Poe, Kimberly Rennie, Tina Reddy, Shawna Rodgers, Saba Khan Siddiki, Daniel Sperry, Patti L. Pierce Tate, Sharon L. Wright, Pablo J. Sánchez, Jonathan L. Slaughter, Leif D. Nelin, Sudarshan R. Jadcherla, Nathalie L. Maitre, Christopher Timan, Keith O. Yeates, Patricia Luzader, Nancy Batterson, Hallie Baugher, Demi R. Beckford, Stephanie Burkhardt, Helen Carey, Michelle Chao, Courtney Cira, Erna Clark, Brittany DeSantis, Christine A. Fortney, Aubrey Fowler, Julie Gutentag, Jennifer L. Grothause, Cole D. Hague, Sarah A. Keim, Katelyn Levengood, Laura Marzec, Jacqueline McCool, Bethany Miller, Mary Ann Nelin, Julia Newton, Courtney Park, Lindsay Pietruszewski, Jessica Purnell, Ruth Seabrook, Julie C. Shadd, Kristi Small, Melanie Stein, Margaret Sullivan, Rox Ann Sullivan, Krystin Warnimont, Lina Yossef-Salameh, Erin Fearns, Abhik Das, Marie G. Gantz, Carla M. Bann, Dennis Wallace, Jeanette O'Donnell Auman, Margaret Crawford, Jenna Gabrio, Jamie E. Newman, Lindsay Parlberg, Carolyn M. Petrie Huitema, Kristin M. Zaterka-Baxter, Krisa P. Van Meurs, Valerie Y. Chock, David K. Stevenson, Susan R. Hintz, Bethany M. Ball, Marian M. Adams, Dona Bahmani, Barbara Bentley, Maria Elena DeAnda, Anne M. DeBattista, Beth Earhart, Lynne C. Huffman, Casey E. Krueger, Ryan E. Lucash, Melinda S. Proud, Elizabeth N. Reichert, Heather Taylor, Hali E. Weiss, Jordan R. Williams, Waldemar A. Carlo, Namasivayam Ambalavanan, Myriam Peralta-Carcelen, Monica V. Collins, Shirley S. Cosby, Kirstin J. Bailey, Fred J. Biasini, Stephanie A. Chopko, Kristy A. Domnanovich, Chantel J. Jno-Finn, Morissa Ladinsky, Mary Beth Moses, Tara E. McNair, Vivien A. Phillips, Julie Preskitt, Richard V. Rector, Kimberlly Stringer, Sally Whitley, Sheree York Chapman, Uday Devaskar, Meena Garg, Isabell B. Purdy, Teresa Chanlaw, Rachel Geller, Tarah T. Colaizy, John A. Widness, Jane E. Brumbaugh, Heidi M. Harmon, Karen J. Johnson, Mendi L. Schmelzel, Jacky R. Walker, Claire A. Goeke, Diane L. Eastman, Michelle L. Baack, Laurie A. Hogden, Megan M. Henning, Chelsey Elenkiwich, Megan Broadbent, Dan L. Ellsbury, Donia B. Bass, Tracy L. Tud, Janell Fuller, Robin K. Ohls, Conra Backstrom Lacy, Carol Hartenberger, Sandra Sundquist Beauman, Mary Hanson, Jean R. Lowe, Elizabeth Kuan, Barbara Schmidt, Haresh Kirpalani, Soraya Abbasi, Aasma S. Chaudhary, Toni Mancini, Dara M. Cucinotta, Judy C. Bernbaum, Marsha Gerdes, Sarvin Ghayam, Hallam Hurt, Jonathan Snyder, Kristina Ziolkowski, Carl T. D'Angio, Ronnie Guillet, Gary J. Myers, Anne Marie Reynolds, Satyan Lakshminrusimha, Holly I.M. Wadkins, Michael G. Sacilowski, Rosemary L. Jensen, Joan Merzbach, William Zorn, Osman Farooq, Dee Maffett, Ashley Williams, Julianne Hunn, Stephanie Guilford, Kelley Yost, Mary Rowan, Diane Prinzing, Karen Wynn, Melissa Bowman, Linda J. Reubens, Ann Marie Scorsone, Michelle Hartley-McAndrew, Caitlin Fallone, Kyle Binion, Constance Orme, Premini Sabaratnam, Alison Kent, Cassandra A. Horihan, Rachel Jones, Elizabeth Boylin, Daisy Rochez, Emily Li, Jennifer Kachelmeyer, Kimberly G. McKee, Kelly R. Coleman, Myra H. Wyckoff, Luc P. Brion, Roy J. Heyne, Diana M. Vasil, Sally S. Adams, Lijun Chen, Maria M. De Leon, Frances Eubanks, Rebecca McDougald, Lara Payageau, Pollieanna Sepulveda, Alicia Guzman, Elizabeth Heyne, Linda A. Madden, Lizette E. Lee, Cathy Twell Boatman, Azucena Vera, Jillian Waterbury, Bradley A. Yoder, Mariana Baserga, Roger G. Faix, Stephen D. Minton, Mark J. Sheffield, Carrie A. Rau, Shawna Baker, Jill Burnett, Susan Christensen, Sean D. Cunningham, Brandy Davis, Jennifer O. Elmont, Becky Hall, Erika R. Jensen, Manndi C. Loertscher, Trisha Marchant, Earl Maxson, Kandace M. McGrath, Hena G. Mickelsen, Galina Morshedzadeh, Melody D. Parry, Susan T. Schaefer, Kelly Stout, Ashley L. Stuart, Kimberlee Weaver-Lewis, Sarah Winter, Kathryn D. Woodbury, Seetha Shankaran, Girija Natarajan, Athina Pappas, Beena G. Sood, Monika Bajaj, Melissa February, Prashant Agarwal, Sanjay Chawla, Rebecca Bara, Kirsten Childs, Eunice Woldt, Laura Goldston, John Barks, Stephanie A. Wiggins, Mary K. Christensen, Martha Carlson, Diane F. White
Journal: JAMA Network Open (2023)

Importance Meta-analyses suggest that corticosteroids may be associated with increased survival without cerebral palsy in infants at high risk of bronchopulmonary dysplasia (BPD) but are associated with adverse neurologic outcomes in low-risk infants. Whether this association exists in contemporary practice is uncertain because most randomized clinical trials administered corticosteroids earlier and at higher doses than currently recommended. Objective To evaluate whether the pretreatment risk of death or grade 2 or 3 BPD at 36 weeks’ postmenstrual age modified the association between postnatal corticosteroid therapy and death or disability at 2 years’ corrected age in extremely preterm infants. Design, Setting, and Participants This cohort study analyzed data on 482 matched pairs of infants from 45 participating US hospitals in the National Institute of Child Health and Human Development Neonatal Research Network Generic Database (GDB). Infants were included in the cohort if they were born at less than 27 weeks’ gestation between April 1, 2011, and March 31, 2017; survived the first 7 postnatal days; and had 2-year death or developmental follow-up data collected between January 2013 and December 2019. Corticosteroid-treated infants were propensity score matched with untreated controls. Data were analyzed from September 1, 2019, to November 30, 2022. Exposure Systemic corticosteroid therapy to prevent BPD that was initiated between day 8 and day 42 after birth. Main Outcomes and Measures The primary outcome was death or moderate to severe neurodevelopmental impairment at 2 years’ corrected age. The secondary outcome was death or moderate to severe cerebral palsy at 2 years’ corrected age. Results A total of 482 matched pairs of infants (mean [SD] gestational age, 24.1 [1.1] weeks]; 270 males [56.0%]) were included from 656 corticosteroid-treated infants and 2796 potential controls. Most treated infants (363 [75.3%]) received dexamethasone. The risk of death or disability associated with corticosteroid therapy was inversely associated with the estimated pretreatment probability of death or grade 2 or 3 BPD. The risk difference for death or neurodevelopmental impairment associated with corticosteroids decreased by 2.7% (95% CI, 1.9%-3.5%) for each 10% increase in the pretreatment risk of death or grade 2 or 3 BPD. This risk transitioned from estimated net harm to benefit when the pretreatment risk of death or grade 2 or 3 BPD exceeded 53% (95% CI, 44%-61%). For death or cerebral palsy, the risk difference decreased by 3.6% (95% CI, 2.9%-4.4%) for each 10% increase in the risk of death or grade 2 or 3 BPD and transitioned from estimated net harm to benefit at a pretreatment risk of 40% (95% CI, 33%-46%). Conclusions and Relevance Results of this study suggested that corticosteroids were associated with a reduced risk of death or disability in infants at moderate to high pretreatment risk of death or grade 2 or 3 BPD but with possible harm in infants at lower risk.